The delay in the onset of action of antidepressant therapies is a major clinical problem. Studies in rats have shown that desensitization of cerebral cortical beta-receptors requires several weeks of treatment with anti-depressant drugs, similar to the time course required for the onset of therapeutic actions. Beta-receptor desensitization is thought to be essential for antidepressant action. Combined treatment with desipramine, a tricyclic antidepressant, and phenoxybenzamine, an alpha-adrenergic receptor blocker, cause a rapid desensitization of cerebral cortical beta-receptors.